ArticleNeoplasia (New York, N.Y.)2009
Differential roles of insulin-like growth factor receptor- and insulin receptor-mediated signaling in the phenotypes of hepatocellular carcinoma cells.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Hepatic IR and IGF1R signaling govern distinct metabolic and carcinogenic processes upon PTEN deficiency in the liver.JHEP reports : innovation in hepatology · 2025Article
- The role of IGF-2 and its variants in enhancing endothelial migration and angiogenesis.Frontiers in cell and developmental biology · 2025Article
- Impairing hydrolase transport machinery prevents human melanoma metastasis.Communications biology · 2024Article
- Insulin receptor alternative splicing in breast and prostate cancer.Cancer cell international · 2024Review
- Influence of polymorphisms in candidate genes on carcass and meat quality traits in rabbits.PloS one · 2023Article
- Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2.Theranostics · 2022Article
- ERK Activation Modulates Cancer Stemness and Motility of a Novel Mouse Oral Squamous Cell Carcinoma Cell Line.Cancers · 2019Article
- Alteration of splicing factors' expression during liver disease progression: impact on hepatocellular carcinoma outcome.Hepatology international · 2019Article
- Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis.International journal of endocrinology · 2019Article
- IGF-I receptor as an emerging potential molecular-targeted for hepatocellular carcinoma in vitro and in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- IGF2 knockdown in two colorectal cancer cell lines decreases survival, adhesion and modulates survival-associated genes.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination.Oncogene · 2016Article
- IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer.Oncotarget · 2016Article
- Comparative transcriptomic analysis reveals the oncogenic fusion protein PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion.Oncogenesis · 2016Article
- Article
- The exploration of network motifs as potential drug targets from post-translational regulatory networks.Scientific reports · 2016Article
- Causal Modeling of Cancer-Stromal Communication Identifies PAPPA as a Novel Stroma-Secreted Factor Activating NFκB Signaling in Hepatocellular Carcinoma.PLoS computational biology · 2015Article
- Role of the Insulin-Like Growth Factor Type 1 Receptor in the Pathogenesis of Diabetic Encephalopathy.International journal of endocrinology · 2015Article
- Aberrant production of tenascin-C in globoid cell leukodystrophy alters psychosine-induced microglial functions.Journal of neuropathology and experimental neurology · 2014Article
- Anti-EGFR antibody conjugated organic-inorganic hybrid lipid nanovesicles selectively target tumor cells.Colloids and surfaces. B, Biointerfaces · 2014Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Intrahepatic and extrahepatic metastases are common findings in hepatocellular carcinoma (HCC). Insulin-like growth factor 2 (IGF2) expression is frequently induced in HCC, and serum IGF2 levels correlate with the presence of extrahepatic metastases. Yet, the role of IGF-induced signaling in the dissemination of HCC remains unclear. We have previously observed elevated IGF2 levels in tumors with metastatic potential in an HCC mouse model. Here, we demonstrate that inhibition of IGF2, or its receptor IGF1R, impairs the migration and invasion activities of murine HCC cells. Furthermore, inhibition of IGF1R also impairs the ability of HCC cells to colonize the lungs after introduction into the circulation through the tail vein but does not impair subcutaneous tumor growth. Collectively, these findings suggest that IGF1R-mediated signaling plays a causative role in tumor dissemination but is not required for tumor growth per se. Although previous studies indicate that IGF ligands can signal through IGF1R/insulin receptor (IR) heterodimers, and IR-A homodimers, we demonstrate that the IR is not required for invasion and metastasis by HCC cells. Finally, we identify matrix metalloproteinase 2 as a mediator of the invasive phenotype downstream of IGF1R-induced signaling. Thus, our studies demonstrate the importance of IGF2-induced signaling in the dissemination of HCC cells.
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